PROJECT SUMMARY Patients who have lost the sense of proprioception demonstrate the necessity of understanding this sense in explaining how the motor system is able to coordinate dexterous movements. An important aspect in understanding any sensory system is the set of transformations that take place in the pathway from simple receptors to rich and useful representations in cortex. In the case of proprioception, knowledge of the early stages of processing are poorly understood. The first proprioceptive synapse in the brain is in the Cuneate Nucleus (CN). Remarkably, encoding of limb state by single CN neurons has never been examined in a non-anesthetized animal before, despite 50 years of behavioral electrophysiology in other brain areas. I propose to record from the CN of an awake behaving monkey to determine how proprioception is encoded in this low-level area. Two main receptor classes comprise the sense of proprioception; muscle spindles and Golgi tendon organs encode muscle lengths and forces respectively. Previous experiments investigating the CN have yielded contradictory results regarding the convergence of signals from multiple muscles and receptor types, contradictions that may be explained by the effects of anesthesia. Anesthesia suppresses cortical activity, which has been shown to send descending signals to brainstem nuclei including CN. Additionally, studies investigating the effects of anesthesia on transmission of proprioceptive signals have found evidence of attenuation of muscle afferents while under surgical sedation. By studying the CN in the awake state, I will remove these effects to better understand both the extent of spatial and modality convergence of neurons in CN, as well as the effects of descending inputs on its transmission of proprioceptive information. I will conduct experiments which answer three aims. First, I will test the effect of anesthesia on the representation of proprioception in single neurons of the CN of a monkey. With selective receptor stimulation, I will characterize the responsiveness of neurons in the CN in both the awake and anesthetized states. Second, using the selective receptor stimulation and encoding models of CN neurons, I will test how single neurons in the CN represent information during reaching behavior. Third, I will compare how the CN represents actively generated movements to those generated by external perturbation, with an attempt to find efference copy in CN. Through these aims, I will answer foundational questions about the role of CN in the afferent proprioceptive pathway.